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Anti-HTLV-1 drug and therapeutic agent for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)

a therapy agent and anti-htlv-1 technology, applied in the field of anti-htlv1 drugs, can solve the problems of further problematic treatment methods

Active Publication Date: 2020-09-15
KAGOSHIMA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0011]According to the present invention, it is possible to provide a therapeutic agent effective for HTLV-1-associated myelopathy for which no effective therapeutic agents have been conventionally available.
[0012]According to the present invention, it is also possible to provide an anti-HTLV-1 drug for reducing HTLV-1 that causes HTLV-1-associated myelopathy.

Problems solved by technology

However, in many cases, the above treatment cannot achieve complete cure, and there are problems such as a rebound phenomenon due to discontinuation of drugs.
The treatment method is further problematic due to side effects such as steroid diabetes, osteoporosis, and immunosuppression.

Method used

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  • Anti-HTLV-1 drug and therapeutic agent for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)
  • Anti-HTLV-1 drug and therapeutic agent for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)
  • Anti-HTLV-1 drug and therapeutic agent for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0078]As mentioned in Experimental Example 1 described below, as a result of microarray analysis and pathway analysis using CD4+ T cells from HTLV-1-associated myelopathy (HAM) patients, pathways including the ABL1 gene were identified as pathways including a gene with a significantly increased expression level in CD4+ T cells from HAM patients. In this Example, imatinib (Glivec / Gleevec) and nilotinib (Tasigna), which are inhibitors of tyrosine kinase encoded by the ABL1 gene, were used to examine the influence of these drugs on CD4+ T cells from HAM patients.

[0079][1] Measurement of the cell concentration of human PBMCs (assay sensitivity determination) by CellTiter-Fluor Cell Viability Assay (G6080, Promega Corporation) (# TB (Technical Bulletin) 371: Instructions for use of Products G6080. G6081, and G6082 (Promega)) (This kit is to quantify the intensity of fluorescence derived from cleavage of a GF-AFC substrate by live cell protease, which is proportional to the number of live...

experimental example 1

[0111]In Experimental Example 1, pathways including genes significantly and increasingly expressed in CD4+ T cells from HTLV-1-associated myelopathy patients were identified by microarray analysis and pathway analysis using CD4+ T cells from HTLV-1-associated myelopathy patients. FIG. 4 depicts the flowchart of the analysis method in this experiment.

[0112]Based on clinical diagnosis according to the WHO diagnostic criteria, 4 cases of HTLV-1-associated myelopathy patients, 4 cases of asymptomatic HTLV-1 carriers (ACs), and 4 cases of HTLV-1 negative healthy controls (NCs) were randomly selected (Table 2). In consideration of ethical issues, blood collection and specimen preservation were carried out with sufficient explanation and written consent. In this study, patients and specimens were anonymized in an unlinkable manner, and specimens obtained under approval from the Ethics Committee of Kagoshima University were used.

[0113]

TABLE 2HAMACNCNumber of specimens444Gender (Male:Female)...

example 2

[0152]In this Example, a novel quantitative determination method, PMA (propidium monoazide)-HTLV-1 viability PCR, by which the proviral load (PVL) of HTLV-1 only in live cells can be quantitatively determined, was developed. This technique was used to examine whether ABL1 inhibitors have an effect of reducing the proviral load of HTLV-1 in living cells. In the usual PVL measurement method, PVL of dead cells and PVL of living cells cannot be distinguished from each other for measurement, meaning that PVL is collectively measured for both cells.

[0153]PMA-HTLV-1 viability PCR, which is a novel quantitative determination method, will be described in detail in Experimental Example 2 below. The method is based on conventionally known PMA viability PCR (Nocker A. et al. J Microbiol Methods 2006. 67: 310-320).

(1) Assay of ABL1 Inhibitors by PMA-HTLV-1 Viability PCR

(1-1) Preparation of Experimentation

(1-1-1) Subjects / Cells

[0154]PBMCs from 16 HAM cases frozen and preserved in liquid nitrogen ...

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Abstract

A novel therapeutic agent and novel anti-HTLV-1 drug for HTLV-1-associated myelopathy / tropical spastic paraparesis (HAM / TSP) is provided. A substance capable of inhibiting tyrosine kinase encoded by the ABL1 gene is contained as an active ingredient.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is the U.S. National Stage of PCT / JP2017 / 028094 filed Aug. 2, 2017, which claims priority to JP 2016-152871, filed Aug. 3, 2016.TECHNICAL FIELD[0002]The present invention relates to an anti-HTLV-1 drug for reducing the load of human T lymphotropic virus type 1 and a therapeutic agent for HTLV-1-associated myelopathy that is a disease caused by the human T lymphotropic virus.BACKGROUND ART[0003]Human T lymphotropic virus type 1 (hereinafter referred to as “HTLV-1”) is a retrovirus that is integrated into the genomic DNA of CD4-positive T lymphocytes and infectiously propagated in vive and between individuals. Tumorigenesis of HTLV-1-infected cells causes adult T cell leukemia (ATL), and HTLV-1-infected cells infiltrate into the spinal cord, thereby inducing HTLV-1-associated myelopathy (HAM / TSP: HTLV-1-associated myelopathy / tropical spastic paraparesis, hereinafter also referred to as “HAM”) which causes spastic spinal par...

Claims

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Application Information

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Patent Type & Authority Patents(United States)
IPC IPC(8): A61K31/506A61P25/00A61K45/00A61P19/00
CPCA61P19/00A61K45/00A61P25/00A61K31/506
Inventor KODAMA, DAISUKEIZUMO, SHUJI
Owner KAGOSHIMA UNIV